Phospholipids are the major lipid components of all cellular membranes. There are two classes of phospholipids: those that have a glycerol backbone and those that contain sphingosine. Both classes are present in the biological membranes. Sphingomyelin is the major sphingosine-containing phospholipid. Its general structure consists of a fatty acid attached to sphingosine by an amide linkage. Phospholipids that contain a glycerol backbone are called phosphoglycerides (or glycerophospholipids); these constitute the most abundant class of phospholipid found in nature. The most abundant types of naturally occurring phosphoglyceride are phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and cardiolipin (Vance, J. E., and Vance, D. E. (2004) Phospholipid biosynthesis in mammalian cells. Biochem Cell Biol., 82, 113-128) The structural diversity within each type of phosphoglyceride is due to the variability of the chain length and degree of saturation of the fatty acid ester groups.
Choline-containing phospholipids have important structural roles in membranes and also play critical roles in cell signaling, either as signaling molecules in their own right or as precursors, through enzymatic hydrolysis, of lipid secondary messengers. Choline is a vitamin, an essential nutrient for most animal cells. Choline enters the cell through specific membrane transporters, and is phosphorylated by choline kinase, after which choline is usually activated as cytidine diphosphate (CDP)-choline (Weiss, S. B., et al. (1958) The enzymatic formation of lecithin from cytidine diphosphate choline and D-1,2-diglyceride. J Biol Chem, 231, 53-64). In the most common pathway for the biosynthesis of choline phospholipids, choline is transferred from CDP-choline to the head group of various phospholipid species, a reaction that takes place in the endoplasmic reticulum. Choline-containing phospholipids are chemically diverse, including phosphatidylcholine, sphingomyelin and ether phospholipids with a choline head group. Phosphatidylcholine is the most abundant phospholipid in most eukaryotic cells, comprising almost 50% of the phospholipid pool. Sphingomyelin is an important component of axonal myelin sheaths, making up 10% of the phospholipids in brain. Choline-containing ether lipids are less abundant, except in white blood cells, in which they reach half the level of phosphatidylcholine (Nagan, N., and Zoeller, R A. (2001) Plasmalogens: biosynthesis and functions, Prog Lipid Res., 40, 199-229), and are precursors of the platelet-activating factor (PAP), a choline phospholipid with potent inflammatory activity.
The cell biology of phospholipids is not well-understood. Progress in understanding the cell biology of choline phospholipids would be greatly aided by having the ability to metabolically label them followed by their high-resolution microscopic imaging in cells.